Biology subjects

Rau, D.

Publications and source records attributed to Rau, D..

4 recordsLinked to original sources

bioRxiv2024

Identification and structural characterization of pseudogenes in Fusarium graminearum.

Pseudogenes provide valuable insight into the evolutionary history of genomes which can be challenging to ascertain through the examination of functional loci alone. This study presents the findings of a comprehensive, two-step genome-wide survey for the identification and characterization of pseudogenes in Fusarium graminearum, the primary causal agent of wheat head blight. By analysing the sequence homology between non-coding regions of the genome and predicted protein sequences, we identified regions with homology to putative paralogous functional sequences. These regions were characterised in terms of their matching sequence structure and position. Most identified pseudogenes were mapped within the fast-evolving genomic compartment and were derived from transposition events. The number of processed and putatively retroposed pseudogenes was found to be comparable. The number of identified pseudogenes was low, which is consistent with the low number of gene duplicates in F. graminearum. No compelling evidence was found to suggest that pseudogene formation can be explained by evolutionary accidents during gene family expansion or as caused by RIP-associated mutagenic events. Notably, about one-third (144/436) of the pseudogenes were found to overlap with untranslated or intron sequences of functional loci, indicating the potential to be transcribed. Using Fusarium comparative genomics, we identified genomic regions with homology to genes lacking functional orthologs in F. graminearum. These were investigated as putative unitary pseudogenes and, in some cases, their original functions were completely lost after the radiation of F. graminearum. Interestingly, the paters of 18 loss-of-function pseudogenes showed homology to domains previously identified in proteins involved in pathogenesis.

genomics↗

bioRxiv2024

Comparative analysis of the genomic architecture of six Fusarium species

Comparative analyses of several plant pathogens have revealed that genome plasticity could be associated with different genomic architectures. In certain species, genomic compartments are characterised by highly conserved regions that contain mainly housekeeping genes and rearranged regions that are enriched for genes related to virulence and adaptation. The compositional and structural characteristics of genomic regions have been significantly associated with compartment membership in single species, but little information is available on the covariation of these features between species. Here, the results of a comparative analysis of the genomic architectures of six agriculturally relevant Fusarium species, which differ for several biological and pathogenic characteristics, are presented. These include F. culmorum, F. fujikoroi, F. graminearum, F. oxysporum, F. solani, and F. verticillioides. The genome sequences of these species were partitioned into adjacent windows, with the average level of gene collinearity with the other species used as an index of compartment membership. High collinearity is typical of conserved regions, while low collinearity is typical of rearranged regions. Several genic and genomic variables were found to be consistently associated with compartment definition among all the Fusarium species that were investigated. The compartment that was characterised by lower collinearity (i.e., high genomic rearrangements) contained more relocated genes, species-specific genes and secreted protein-encoding genes than regions with low collinearity. Furthermore, several molecular evidence indicates that low-collinearity regions are more likely to be subjected to selective pressure than high-collinearity regions. Indeed, genes residing in the former regions exhibited higher rates of sequence evolution than in the latter, as indicated by the high non-synonymous-to-synonymous substitution rates. However, they exhibited signatures of selection to minimise the costs of transcription, as indicated by their high coding density. Our data suggests that although variable genomic compartments evolved mostly after species radiation, they share similar genomic features across related species and perhaps evolve with similar mechanisms.

evolutionary biology↗

bioRxiv2022

Towards generalizable prediction of antibody thermostability using machine learning on sequence and structure features

Over the last three decades, the appeal for monoclonal antibodies (mAbs) as therapeutics has been steadily increasing as evident with FDAs recent landmark approval of the 100th mAb. Unlike mAbs that bind to single targets, multispecific biologics (bsAbs) with their single-chain variable fragment (scFv) modules have garnered particular interest owing to the advantage of engaging distinct targets. Despite their exquisite specificity and affinity, the relatively poor thermostability of these scFv modules often hampers their development as a potential therapeutic drug. In recent years, engineering antibody sequences to enhance their stability by mutations has gained considerable momentum. As experimental methods for antibody engineering are time-intensive, laborious, and expensive, computational methods serve as a fast and inexpensive alternative to conventional routes. In this work, we show two machine learning methods - one with pre-trained language models (PTLM) capturing functional effects of sequence variation, and second, a supervised convolutional neural network (CNN) trained with Rosetta energetic features - to better classify thermostable scFv variants from sequence. Both these models are trained over temperature-specific data (TS50 measurements) derived from multiple libraries of scFv sequences. In this work, we show that a sufficiently simple CNN model trained with energetic features generalizes better than a pre-trained language model on out-of-distribution (blind) sequences (average Spearman correlation coefficient of 0.4 as opposed to 0.15). Further, we demonstrate that for an independent mAb with available thermal melting temperatures for 20 experimentally characterized thermostable mutations, these models trained on TS50 data could identify 18 residue positions and 5 identical amino-acid mutations showing remarkable generalizability. Our results suggest that such models can be broadly applicable for improving the biological characteristics of antibodies. Further, transferring such models for alternative physico-chemical properties of scFvs can have potential applications in optimizing large-scale production and delivery of mAbs or bsAbs.

bioinformatics↗

bioRxiv2020

Pod indehiscence in common bean is associated to the fine regulation of PvMYB26 and a non-functional abscission layer

In legumes, pod shattering occurs when mature pods dehisce along the sutures, and detachment of the valves promotes seed dispersal. In Phaseolus vulgaris, the major locus qPD5.1-Pv for pod indehiscence was identified recently. We developed a BC4/F4 introgression line population and narrowed the major locus down to a 22.5-kb region. Here, gene expression and a parallel histological analysis of dehiscent and indehiscent pods identified an AtMYB26 orthologue as the best candidate for loss of pod shattering, on a genomic region ~11 kb downstream of the highest associated peak. Based on mapping and expression data, we propose early and fine up-regulation of PvMYB26 in dehiscent pods. Detailed histological analysis establishes that pod indehiscence is associated to the lack of a functional abscission layer in the ventral sheath, and that the key anatomical modifications associated with pod shattering in common bean occur early during pod development. We finally propose that loss of pod shattering in legumes resulted from histological convergent evolution and that this is the result of selection at orthologous loci. One-sentence summaryA non-functional abscission layer determines the loss of pod shattering; mapping data, and parallel gene expression and histological analysis support PvMYB26 as the candidate gene for pod indehiscence.

genetics↗